MMP9 mediates acute hyperglycemia-induced human cardiac stem cell death by upregulating apoptosis and pyroptosis in vitro

Yadav, Santosh K.; Kambis, Tyler N.; Kar, Sumit; Park, Song Y.; Mishra, Paras Kumar

doi:10.1038/s41419-020-2367-6

Cited by 56 publications

(52 citation statements)

References 42 publications

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“…It was recently shown that the role of MMP-9 in hyperglycemia-induced cell death in human cardiac stem cells showed MMP-9 initiates apoptosis irrespective of hyperglycemia and determines MMP-9 upstream to SAPK/JNK signaling and demonstrated MMP-9-mediated apoptosis. This study also reveals that MMP-9 is upstream to MAP/JNK signaling and plays a major role in hyperglycemia-induced ROS generation in human cardiac stem cells (Yadav et al 2020). Briefly, MMP-9 has a pivotal role in cell survival.…”

Section: Discussionmentioning

confidence: 55%

“…MTT assay was employed to measure the toxicity in cancer and healthy cells caused by nanoparticle's exposure to find the lethal toxic dose. Also, toxicity in cells caused by nanoparticles was further assessed for the Apoptotic pathway and the regulation of metalloprotease enzymes, which are crucial in the cell death pathway (Kessenbrock et al 2010;Yadav et al 2020). The possible mechanism of toxicity lead by Ag-NP or Cu-NP is mainly by oxidative stress, DNA damage and lipid peroxidation, involving apoptosis or autophagy cell death pathway.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and analysis of silver–copper alloy nanoparticles of different ratios manifest anticancer activity in breast cancer cells

et al. 2020

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Background Breast cancer is therapeutically very challenging to treat as it has the main four known genetic alterations, which result in the existence of several phenotypes leading to the difference in the mode of therapy and with poor outcome. Metallic nanoparticles of silver or copper have been studied previously as anticancer agents in breast cancer and other types of cancers. However, the anticancer effect of silver–copper alloy nanoparticles (AgCu-NP) is not studied in breast cancer. In this study, we aim to synthesize silver nanoparticles (Ag-NP), or copper nanoparticles (Cu-NP), and AgCu-NP and evaluate their toxicity in breast cancer and healthy breast cells. Results We synthesized sodium citrate and mercapto-propionic acid (MPA-3) capped water-soluble metallic nanoparticles of Ag-NP or Cu-NP and an alloy of three different combinations of AgCu-NP. High-resolution transmission electron microscopy characterization of nanoparticles revealed the spherical shape nanoparticles of varied sizes, furthermore dynamic light scattering characterization was performed, which investigated the hydrodynamic size and stability in phosphate buffer solution. Energy-dispersive X-ray spectroscopy (EDS) measurements were obtained from the transmission electron microscope to study the composition of alloy nanoparticles and the distribution pattern of silver and copper in the alloy nanoparticles. We measured the toxicity of nanoparticles to breast cancer MCF-7 cell line by MTT assay and compared the toxic effect with non-cancerous breast epithelial cells MCF-10A. Our data showed that Ag-NP or Cu-NP have no effect on cancer cells or healthy cells, except Ag-NP at 20 µg/ml were toxic to cancer cells. However, AgCu-NP were significantly toxic to MCF-7 cells at 10 µg/ml concentration, while as AgCu-NP have no toxic effect on healthy cells. Furthermore, we observed the cell death pathway by the apoptosis marker Annexin-V which showed non-significant results, while the exposure of AgCu-NP in MCF-7 cells leads to toxicity and also caused significant increase in MMP-9 level, which suggests the cell death may be associated with other pathways such as autophagy and oxidative stress related. Conclusion The data suggest that the AgCu-NP alloy imposes preferential toxicity in breast cancer MCF-7 cells and thus could be exploited as a new candidate for further anticancer investigation

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Section: Discussionmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Synthesis and analysis of silver–copper alloy nanoparticles of different ratios manifest anticancer activity in breast cancer cells

et al. 2020

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“…To determine the role of MMP9 in epigenetic modifications in hCSCs, we created and validated MMP9 knockout (MMP9KO) hCSCs by CRISPR-Cas9 method 18 ( Figure S1A-D). To determine whether MMP9 mediates epigenetic modifications, we measured protein levels of canonical DNMT1 and DNMT3a in the control and MMP9KO hCSCs.…”

Section: Resultsmentioning

confidence: 99%

“…However, the activity of MMP9 was higher in the HG medium ( Figure S1E), which was consistent with our previous report. 18 We supplemented MMP9 by adding HG or NG culture medium to the MMP9KO hCSCs for 24 hours. To determine the paracrine effects of MMP9 on epigenetic modifications and autophagy in the MMP9KO hCSCs, we compared the levels of DNMT3a, H3K9me1, H3K9me2 HDAC1, SIRT1, LC3BII, and p62 in untreated MMP9KO hCSCs to the HG-medium treated MMP9KO and control hCSCs.…”

Section: Histone Deacetylation Causes Chromatin Condensation Andmentioning

confidence: 99%

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Intracellular matrix metalloproteinase-9 mediates epigenetic modifications and autophagy to regulate differentiation in human cardiac stem cells

Yadav

Mishra

2021

Stem Cells

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Epigenetic reprogramming and autophagy have critical roles in differentiation of stem cells. However, very little is known about how epigenetic modifications are mediated and how they contribute to autophagy and differentiation in human cardiac stem cells (hCSCs). Previously, we have reported that intracellular matrix metalloproteinase-9 (MMP9), a collagenase, mediates cell death in hCSCs. Here, we investigated whether intracellular MMP9 mediates epigenetic modifications and autophagy in hCSCs. We created MMP9KO hCSCs and treated them with 5-azacytidine, an inhibitor of DNA methylation, and bafilomycin A1, an inhibitor of autophagosome degradation, and evaluated epigenetic modifications, autophagic flux, and differentiation. Our results showed compromised epigenetic modifications, reduced autophagy, and impaired differentiation in MMP9KO hCSCs.Remarkably, paracrine MMP9 supplementation restored epigenetic modifications but further reduced autophagy in MMP9KO hCSCs. We conclude that intracellular MMP9 is a critical mediator of epigenetic modifications and autophagy in hCSCs. Furthermore, the endocrine and paracrine effects of MMP9 vary for regulating autophagy in hCSCs. These novel roles of MMP9 are valuable for stem cell therapy.

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Protective Mechanism of Ethyl Gallate against Intestinal Ischemia‐Reperfusion Injury in Mice by in Vivo and in Vitro Studies Based on Transcriptomics

Fan

Yan

et al. 2022

Chemistry & Biodiversity

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Intestinal ischemia‐reperfusion injury (IIRI) is a common clinical disease that can be life‐threatening in severe cases. This study aimed to investigate the effects of ethyl gallate (EG) on IIRI and its underlying mechanisms. A mouse model was established to mimic human IIRI by clamping the superior mesenteric artery. Transcriptomics techniques were used in conjunction with experiments to explore the potential mechanisms of EG action. Intestinal histomorphological damage, including intestinal villi damage and mucosal hemorrhage, was significantly reversed by EG. EG also alleviated the oxidative stress, inflammation, and intestinal epithelial apoptosis caused by IIRI. 2592 up‐regulated genes and 2754 down‐regulated genes were identified after EG treatment, and these differential genes were enriched in signaling pathways, including fat digestion and absorption, and extracellular matrix (ECM) receptor interactions. In IIRI mouse intestinal tissue, expression of the differential protein matrix metalloproteinase 9 (MMP9), as well as its co‐protein NF‐κB‐p65, was significantly increased, while EG inhibited the expression of MMP9 and NF‐κB‐p65. In Caco‐2 cells in an established oxygen‐glucose deprivation/reperfusion model (OGD/R), EG significantly reversed the decrease in intestinal barrier trans‐epithelial electrical resistance (TEER). However, in the presence of MMP9 inhibitors, EG did not reverse the decreasing trend in TEER. This study illustrates the protective effect and mechanism of action of EG on IIRI and, combined with in vivo and in vitro experiments, it reveals that MMP9 may be the main target of EG action. This study provides new scientific information on the therapeutic effects of EG on IIRI.

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MMP9 mediates acute hyperglycemia-induced human cardiac stem cell death by upregulating apoptosis and pyroptosis in vitro

Cited by 56 publications

References 42 publications

Synthesis and analysis of silver–copper alloy nanoparticles of different ratios manifest anticancer activity in breast cancer cells

Synthesis and analysis of silver–copper alloy nanoparticles of different ratios manifest anticancer activity in breast cancer cells

Intracellular matrix metalloproteinase-9 mediates epigenetic modifications and autophagy to regulate differentiation in human cardiac stem cells

Protective Mechanism of Ethyl Gallate against Intestinal Ischemia‐Reperfusion Injury in Mice by in Vivo and in Vitro Studies Based on Transcriptomics

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